OVERALL DESCRIPTION Despite recent treatment improvements, ovarian cancer remains the number one gynecologic killer in the United States. An expanded translational research effort is necessary to identify new opportunities for diagnosis, prevention, and treatment. The FCCC Specialized Program of Research Excellence (SPORE) in Ovarian Cancer consists of seven research projects, a Developmental Research Program, a Career Development Program, and four specialized cores to support the research programs. The projects are interrelated and are focused on ovarian carcinogenesis and ovarian cancer prevention and treatment: (1) Determination of Molecular Pathways Regulating LOT1 mediated growth suppression; (2) Bio-markers of Ovarian Cancer and the Molecular Genetics Analysis of Human Ovarian Surface Epithelial (HOSE) Cell Transformation; (3) The Role of Principal Investigator 3-Kinase/AKT2 Signaling in Ovarian Oncogenesis; (4) Chemoprevention Studies in Patients at Risk for Ovarian Cancer; (5) Role of DNA-Dependent Protein Kinase in Ovarian Cancer Drug Resistance; (6) Pharmacokinetic- Pharmacodynamic Models to Design and Optimize Clinical Trials in Ovarian Cancer; (7) The Development of an Ovarian-Selective Replicating Adenoviral Vector for use in Gene Therapy for Ovarian Cancer. The last project is in collaboration with the Institute for Human Gene Therapy at the University of Pennsylvania. The specialized cores include the establishment of an OCCN which links FCCC together with the University of Pennsylvania, Hershey Medical Center, Cancer Institute of New Jersey, and other participating institutions to increase accrual to chemoprevention trials for women at high risk for ovarian cancer and to therapeutic trials for women diagnosed with this disease. The Tissue Procurement Core will process bio-specimens for molecular studies on oncogenesis and drug resistance. The Genetics Susceptibility Testing Laboratory will screen patients for BRCA1 mutations in order to identify individuals who are eligible for participation in the clinical trial of fenretinide vs. placebo (Project 3). The Administration/Biostatistical Core will provide administrative and biostatistical support for laboratory projects, clinical trials, and for the other cores. FCCC has had a long-term commitment to research in ovarian cancer and will provide additional institutional resources to support the goals of this SPORE application. Senior leadership of the Center is directly involved in the SPORE application. The Principal Investigator is the Senior Vice President for Medical Science. The Co-Principal Investigator is Program Leader in the CCSG Ovarian Cancer Program and the President of the Center serves on the Executive Committee. This SPORE Program is a multidisciplinary collaboration of laboratory researchers and clinicians focused on decreasing morbidity and mortality from this disease. This goal will be accomplished by prevention strategies based on an understanding of ovarian oncogenesis coupled with novel scientifically based therapeutic approaches.